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A Kinetic Model of the Monocarboxylate Transporter MCT1 and its Interaction with Carbonic Anhydrase II

Joachim Almquist (Institutionen för kemi- och bioteknik, Systembiologi) ; Patrick Lang ; Dieter Prätzel-Wolters ; Joachim W. Deitmer ; Mats Jirstrand (Institutionen för kemi- och bioteknik, Systembiologi) ; Holger M. Becker
Journal of Computer Science and Systems Biology (0974–7230). Vol. 3 (2010), 5, p. 107-116.
[Artikel, refereegranskad vetenskaplig]

The enzyme carbonic anhydrase isoform II (CAII), catalyzing the hydration and dehy-dration of CO2, enhances transport activity of the monocarboxylate transporter isoform I (MCT1, SLC16A1) expressed in Xenopus oocytes by a mechanism that does not require CAII catalytic activity. In the present study, we have investigated the mechanism of the CAII induced increase in transport activity by using electrophysiological techniques and mathematical modeling of the MCT1 transport cycle. The model consists of six states arranged in cyclic fashion and features an ordered, mirrorsymmetric, binding mechanism, where binding and unbinding of the proton to the transport protein is considered to be the rate limiting step under physiological conditions. An explicit rate expression for the substrate flux is derived using model reduction techniques. By treating the pools of intra-and extracellular MCT1 substrates as dynamic states, the time dependent kinetics are obtained by integration, using the derived expression for the substrate flux. The simulations were compared with experimental data obtained from MCT1-expressing oocytes injected with different amounts of CAII. The model suggests that CAII increases the effective rate constants of the proton reactions, possibly by working as a proton antenna.

Nyckelord: CAII, Mathematical modeling, Model reduction, Electrophysiology, pH-sensitive microelectrodes, Proton antenna


http://dx.doi.org/10.4172/jcsb.1000066



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Denna post skapades 2011-01-14. Senast ändrad 2014-12-09.
CPL Pubid: 133864

 

Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Systembiologi (2008-2014)

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Systemteknik
Molekylärbiologi
Cell- och molekylärbiologi
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Molekylär neurobiologi

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